Indolent NK-cell lymphoproliferative disorder of the gastrointestinal tract

Indolent natural killer (NK)-cell lymphoproliferative disorder of the gastrointestinal tract (previously known as NK-cell enteropathy) is a benign proliferation of NK cells. The exact cause is unknown, but it may be a localized immune reaction. Patients may be asymptomatic or present with nonspecific gastrointestinal symptoms (e.g., abdominal pain, diarrhea). Diagnosis involves endoscopy with biopsies. The condition is typically indolent, and a watch-and-wait approach is generally recommended.

Indolent NK-cell lymphoproliferative disorder of the gastrointestinal tract, previously known as NK-cell enteropathy, is a rare and benign proliferation of NK cells in the gastrointestinal tract.^[1][2]

• Median age at diagnosis: 46 years ^[1][3]
• Sex: ♀ > ♂ ^[1][3]

Epidemiological data refers to the US, unless otherwise specified.

• The exact etiology is unknown.^[1][3]
• It may involve a localized immune reaction or response to inflammation.^[1]

• Patients may be asymptomatic or present with nonspecific gastrointestinal symptoms, e.g.:^[1][3]
  • Abdominal pain or discomfort
  • Diarrhea
  • Constipation
  • Rectal bleeding
  • Weight loss
• Physical examination typically shows no evidence of lymphadenopathy or organomegaly.^[1]

Diagnosis is specialist-guided using endoscopy with multiple mucosal biopsies.

• Endoscopy findings: Findings may include superficial ulcers or mucosal hemorrhages in one or more sites of the gastrointestinal tract.^{[1] [3]}
• Histopathology: typically shows dense infiltrate of atypical lymphoid cells ^[4]
• Immunophenotype: Atypical cells have a characteristic NK-cell phenotype with typical markers (e.g., CD56⁺, cytoplasmic CD3⁺, CD7⁺, EBV^_). ^[4]
• Molecular genetics: may show JAK3 mutations ^[5]

Differentiation from lymphoma is essential to avoid unnecessary and potentially harmful chemotherapy.

• Inflammatory bowel disease
• Intestinal lymphomas
  • Extranodal NK/T-cell lymphoma ^[4]
  • Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL)^[4]
  • Enteropathy-associated T-cell lymphoma (EATL)
  • MALT lymphoma
• Indolent T-cell lymphoproliferative disorder of the gastrointestinal tract
• See also:
  • “Differential diagnoses of abdominal pain”
  • “Differential diagnoses of diarrhea”

The differential diagnoses listed here are not exhaustive.

• There is no specific treatment.
• Management should be specialist-guided.
• A conservative, watch-and-wait approach is generally recommended.^[1]

The clinical course is typically indolent; lesions may persist, recur, or spontaneously regress.^[3][4]